In conducting nucleic acid analyses based on recognition of differentially labeled nucleotides or nucleic targets, the purity of the labeled nucleotides or targets can be of paramount importance. While the conventional methods of labeling a nucleotide or polynucleotide and the methods for purifying these labeled molecules are well-developed, the efficiencies for both the labeling and purification techniques are less than perfect and will tend to result in compositions that are not hundred percent pure. The presence of unlabeled nucleotides or targets in sequencing or hybridization reaction mixtures, respectively, can result in high background noise signals, result in errors in base calling or in detection of a specific hybridization event, and cause other difficulties in different types of analyses. The problem of impure nucleotide compositions can be particularly exacerbated in nucleic acid analyses such as single-molecule sequencing or hybridization that require high-resolution detection of the labeled nucleotides or labeled nucleic acid targets. In case of single-molecule sequencing, the problem can stem from the tendency of many polymerase enzymes to exhibit a preference for natural nucleotides over the labeled nucleotide analogs. This preference can be as much as a hundred-fold or more, resulting in a large fraction of missed bases even for small impurity levels in the mix.
Thus, there remains a considerable need for improved nucleotide and nucleic acid compositions particularly suited for high-resolution sequencing and hybridization assays.